Patent DE-102008014077-A1 (DE)
Title: New borrelidin derivatives are janus kinase 3 inhibitors useful e.g. for treating tumor, microbial infection, immune disorder and ophthalmic disease, inhibiting angiogenesis, and manufacturing herbicides and insecticides against arthropods
Inventor: SIMON WERNER
IPC: C07D405/04
Filed: 2008-03-13
Abstract: Borrelidin derivatives (I) and their stereoisomers, tautomers and salts are new. Borrelidin derivatives of formula (I) and their stereoisomers, tautomers and salts are new. Either A : =O, =N-X-R1, =N-R1, H,OR3, H,N-R1, HO,R2, H,F or F,F; and B1 : =N-OH, =N-O-R1, H,R1, OH,R2, =CR4R4 or halo; or AB1 : 5 or 6 membered saturated or partially unsaturated or aromatic heterocycle with 2 or 3 heteroatom comprising N, O or S (optionally substituted with R19); D : COOH, CH 2OH, CONH 2, CSNH 2, CONHOH, COOR16, CH 2OR16, CONHR16, CONR16R17, CONHOR16 or CONHNHR16; X : O, NH(CO), NH(CO)NH or NR14; E : CN, CONH 2, CSNH 2, COOH, COOR18, CHO, CH=NOR18 or 5- or 6-membered aromatic heterocycle with 1-4 heteroatom (optionally substituted with R20); R1 : H, 1-14C alkyl, 2-14C alkenyl, 1-4C alkyl-aryl, heteroaryl, 1-4C alkyl-heteroaryl, cycloalkyl, 1-4C alkyl-cycloalkyl, heterocycloalkyl, 1-4C alkyl-heterocycloalkyl, cycloalkyl-aryl, 1-4C alkyl-cycloalkyl-aryl, heterocycloalkyl-aryl, 1-4C alkyl-heterocycloalkyl-aryl, cycloalkyl-heteroaryl, 1-4C alkyl-cycloalkyl-heteroaryl, heterocycloalkyl-heteroaryl, 1-4C alkyl-heterocycloalkyl-heteroaryl, C mH 2 m + o - pY1 p, 1-10C alkanoyl, 1-10C alkanoyl-aryl, 1-10C alkanoyl-heteroaryl, (hetero)aryloyl or T; T : (CH 2) rCH 2NHCOR11, (CH 2) rCH 2OCOR11, (CH 2) rCH 2NHCSR11, (CH 2) rCH 2S(O) nR11, (CH 2) rCH 2SCOR11, (CH 2) rCH 2OSO 2-R11, (CH 2) rCHO, (CH 2) rCH=NOH, (CH 2) rCH(OH)R11, (CH 2) rCH=NOR11, (CH 2) rCH=NOCOR11, (CH 2) rCH=NOCH 2CONR11R12, (CH 2) rCH=NOCH(CH 3)CONR11R12, (CH 2) rCH=NOC(CH 3) 2CONR11R12, (CH 2) rCH=N-NHCO-R13, (CH 2) rCH=N-NHC(O)NH-R13, (CH 2) rCH=N-NHC(S)NH-R13, (CH 2) rCH=N-NHC(NH)NH-R13, (CH 2) rCH=N-NHC(NH)-R13, (CH 2) rCH=N-NH-CO-CH 2NHCOR11, (CH 2) rCH=N-O-CH 2NHCOR11, (CH 2) rCH=N-NHCS-R13, (CH 2) rCH=CR15R16 (trans or cis), (CH 2) rCOOH, (CH 2) rCOOR11, (CH 2) rCONR11R12, (CH 2) rCH=NR11, (CH 2) rCH=N-NR11R12, (CH 2) rCH=N-NHSO 2-aryl or (CH 2) rCH=N-NHSO 2-heteroaryl; n : 0-2; r : 1-5; R2 : 1-14C alkyl, 1-14C alkanoyl, 1-6C alkylhydroxy, 1-6C alkoxy, 1-6C alkylamino, 1-6C alkylamino-1-6C-alkyl, 1-6C alkylamino-di-1-6C alkyl, cycloalkyl, 1-4C alkyl-cycloalkyl, heterocycloalkyl, 1-4C alkyl-heterocycloalkyl, aryl, aryloyl, 1-4C alkyl-aryl, heteroaryl, heteroaryloyl, 1-4C alkyl-heteroaryl, cycloalkanoyl, 1-4C alkanoyl-cycloalkyl, heterocycloalkanoyl, 1-4C alkanoyl-heterocycloalkyl, 1-4C alkanoyl-aryl, 1-4C alkanoyl-heteroaryl, NH 2or NHCOR11; R3 : 1-14C alkyl, 2-14C alkenyl, 1-4C alkyl-aryl, heteroaryl, 1-4C alkyl-heteroaryl, cycloalkyl, 1-4C alkyl-cycloalkyl, heterocycloalkyl, 1-4C alkyl-heterocycloalkyl, C mH 2 m + o - pY1 p, 1-10C alkanoyl, aryl-1-10C alkanoyl, heteroaryl-1-10C alkanoyl, (hetero)aryloyl or T; R4 : H or R2; R11, R12 : H, 1-14C alkyl, 1-14C alkanoyl, 1-6C alkylhydroxy, 1-6C alkoxy, 1-6C alkylamino, 1-6C alkylamino-1-6C alkyl, 1-6C alkylamino-di-1-6C alkyl, cycloalkyl, 1-4C alkyl-cycloalkyl, heterocycloalkyl, 1-4C alkyl-heterocycloalkyl, aryl, aryloyl, 1-4C alkyl-aryl, heteroaryl, heteroaryloyl, 1-4C alkyl-heteroaryl, cycloalkanoyl, 1-4C alkanoyl-cycloalkyl, heterocycloalkanoyl, 1-4C alkanoyl-heterocycloalkyl, 1-4C alkanoyl-aryl, 1-4C alkanoyl-heteroaryl, mono- and di-sugar residue that are linked via a carbon atom and carrying OH group, where the sugar is glucuronic acid and its stereoisomers at all optical carbon atoms, aldopentose, aldohexose including their deoxy compounds (such as glucose, deoxyglucose, ribose or deoxyribose); R13 : R11, CH 2-pyridinium salt, CH 2-tri-1-6C alkyl-ammonium-salt, CONH 2, CSNH 2, CN or CH 2CN; R14, R19, R20 : R1; R15 : R11, H, CN, COCH 3, COOH, COOR11, CONR11R12, NH 2or NHCOR11; R16 : 1-14C alkyl, 2-14C alkenyl, 1-4C alkyl-aryl, heteroaryl, 1-4C alkyl-heteroaryl, cycloalkyl, 1-4C alkyl-cycloalkyl, heterocycloalkyl, 1-4C alkyl-heterocycloalkyl, C mH 2 m + o - pY1 por T; R17, R18 : R16; and bond with dotted line : chemically stable double bond; Y1 : halo, OH, OR11, NH 2, NHR11, NR11R12, SH, SR11 or CN; m : 1-6; o : 1, -1 or -2; and p : 1-2m+o. Provided that: when m is 1-6, then o is 1; when m is 2-6, then o is -1; and when m is 4-6, then o is -2. An independent claim is included for a medicament comprising (I), and usual carrier and auxiliary material. [Image] ACTIVITY : Cytostatic; Antimicrobial; Immunomodulator; Angiogenesis inhibitor; Herbicide; Insecticide; Arthropodicide; Antiarthritic; Antirheumatic; Antipsoriatic; Antiarteriosclerotic; Ophthalmological. MECHANISM OF ACTION : Janus kinase 3 inhibitor.